Our Built-In “Antioxidant” System

Antioxidants have been in the popular press for more than 20 years and, while many people may not understand what exactly antioxidants do, they have the right idea that consuming foods known to contain high levels of the compounds is better than not consuming them. In its simplest form, an antioxidant is a compound that can be consumed or that the body makes to defend against damaging effects of free radicals, highly reactive molecules that can damage cells and tissues. We are exposed to free radicals through everyday living.

The antioxidant properties of fruits and vegetables are commonly ascribed to their high content of special nutrients, such as polyphenols, vitamins C and E, and beta-carotene. These nutrients function by reacting with free radicals to prevent them from causing cellular damage. Recent work from Dr. Steven Zeisel’s laboratory at the NRI, however, suggests that much of the antioxidant effect of these foods when eaten in fact arises from compounds not directly involved in free-radical scavenging.

Our cells have built-in systems that protect against free-radical damage. Activation of these systems requires expression of a group of genes involved in the antioxidant response; expression is regulated by so-called antioxidant response elements (AREs). Activation of AREs is, therefore, a key part of the body’s response to oxidative stress. The ability to trigger our built-in antioxidant systems is not typically taken into consideration when describing the antioxidant capacity of particular nutrients. Rather, their antioxidant properties are determined by analysis of their structure or by their ability to deactivate oxygen radicals. In contrast, Zeisel’s group has directly tested the ability of food and vegetable extracts to activate AREs. They found numerous extracts that are able to activate AREs, and hence the cellular defense systems, but which do not themselves exhibit strong antioxidant capacity.

In their recent Journal of Nutrition publication, Zeisel’s group isolated 134 extracts from the flesh and peels of various fruits and vegetables. These extracts were tested for their ability to activate AREs and also for their direct antioxidant properties. Because polyphenols have been historically associated with fruit and vegetable antioxidant properties, the extracts were also analyzed for polyphenol content. The results showed that neither direct antioxidant activity nor polyphenol content correlated with the ability of an extract to activate AREs. For instance, carrots and pineapple rank above the 97th percentile for ARE activation, but are in the lower quartile when ranked by traditional measures of antioxidant activity. Overall, the traditional measurements of a molecule’s antioxidant capacity fail to predict whether that molecule will stimulate the cell’s antioxidant response. Because current efforts to isolate (and market) nutritional antioxidants use the traditional measurement methods, they are very likely to miss important nutrients that can activate our own antioxidant defenses.

What this means for you

The described studies were carried out using individual cells, not humans, so it is not known whether eating these fruits and vegetables will have the same effect. The NRI has started clinical trials to directly determine whether consuming fruit and vegetable extracts also results in activation of the body’s antioxidant defense systems.

Also, because the described study used unpurified extracts, we don’t know yet which specific molecules activate AREs. Further studies are planned to identify the active compounds. In the meantime, eat your carrots!